Strontium-90 (90Sr), which is present in radioactive fallout, has a half-life of approximately 29 years (typically reported at values ranging from 28.5 to 29.1 years), and decays by high energy electron emission (β particle emission). Strontium-90 ions can be detected in the urine of subjects exposed to such fallout. Strontium tends to migrate to human bone structures, replacing calcium, and once absorbed, is difficult to eliminate. Long term accumulation of 90Sr has been shown to produce bone cancer.
Quantifying the ingestion of radioactivity is difficult. Biological indicators are only useful in the most extreme of exposures since the body can tolerate large doses of radioactivity. For some radionuclides that emit high energy gamma rays, one can use specialized radioactive counters that can count the entire human body. For radionuclides that emit alpha or beta particles or low energy gamma rays only, this type of counting is useless. Moreover, these facilities are few and far between and only available at very specialized centers. The standard technique is to analyze urine since the blood-urine pathway is common to all ingestions.
Health physicists use methods to quantify the dose burden to the body based on quantities measured in urine after a known number of days following exposure. The methods are based on gamma or beta-alpha counting of urine samples. For quantifying gamma-emitting isotopes (e.g., 137Cs) direct counting of urine samples works well since the gamma ray is able to easily transmit through the urine, the vial, and penetrate the active region of the detector. For beta-emitters like 90Sr or alpha emitters like many of the actinide isotopes, the standard method is liquid scintillation counting.
In liquid scintillation, an aliquot of the liquid sample is dissolved into a scintillation cocktail solution, which is a specially formulated solution that converts the beta and alpha ray energies into visible light pulses that are captured by the detector. Such scintillation solutions are well known in the art. However, care must be taken to quantify the quenching factor of such solution-cocktail mixtures. Quenching of radiation-induced luminescence of the fluorophores of the cocktail reduces the overall number of photons that reach the detector below the expected value based on total radioactive decay events. Both colored and non-colored materials can quench a sample. Certain electronegative species in solution can chemically disrupt the energy conversion process and eliminate the formation of the visible light pulse that is used for detection. Colored materials in solution can absorb or scatter the light pulse before it escapes from solution, thereby preventing its detection. Acidified urine is particularly troublesome because it contains both colored and colorless quenching agents. As a result, to count 90Sr (pure beta emitter) by the standard method (liquid scintillation counting), the 90Sr must be purified from the urine. The method for purification must separate the 90Sr from the organic and other chemicals dissolved in the urine, and also the other radioactive and non-radioactive ions that are present. The non-radioactive ions need to be removed for practical reasons since they will usually overload a separations column and prevent the 90Sr from being purified. To add difficulty, 90Sr decays to a very short lived daughter isotope 90Y that also emits a beta-particle. Because the 90Y is so short-lived, the number of radioactive emissions (beta emissions) is comparable to the number of 90Sr emissions. So, if an analytical method does not separate the 90Y from the 90Sr, the total counts by liquid scintillation will be grossly over-estimated and so will the resulting dose burden that is calculated. Radioactive 40K presents a similar problem, because it is present as a trace isotope of natural potassium in the urine.
Normal human urine is an aqueous solution containing a number of organic materials (e.g., urea, creatinine, uric acid and smaller amounts of carbohydrates, enzymes, fatty acids, hormones, pigments, mucins, etc.) and ions (e.g., sodium, potassium, calcium, etc.) that can vary greatly between individuals and is highly dependent upon diet. In addition, typical concentrations of metal ions in urine are high (e.g., about 0.1 M Na+, 0.03 M K+, and 0.005 M Ca2+) compared to the trace quantities of strontium that might be found in urine samples. Thus, any practical method for extracting 90Sr from urine would require high capacity (where selectivity toward strontium is poor) or high selectivity (where the quantity of the extractant must be kept low). In practice, experimental protocols generally involve precipitation of alkaline earth metal ions from the urine and ashing of the precipitate to eliminate organic molecules, followed by elemental separations. This process is time-consuming, and requires a skilled technician, but is necessary to ensure quantitative recovery of strontium. However, when many samples have to be analyzed quickly, such as after a massive release of radioactive material, quantitative recovery of strontium may not be of primary importance, so long as one can ensure good, predictable recovery with a faster method.
Elimination of the ashing step in the prior reported methods has been proposed. In one reported alternative method, urine was diluted 5-fold with 0.1 M aqueous HNO3 with about 1% of a poly(ethylene glycol) added, and solvent extraction with the acidic form of dicarbolide in nitrobenzene provided a high strontium distribution coefficient (D(Sr)>300) and high strontium selectivity over sodium (D(Sr)/D(Na)>800). The number of steps involved for extraction and purification is relatively high, and such solvent extraction methods are not readily scalable for large numbers of samples. The Center for Disease Control (CDC) has expressed a desire for a target analysis throughput of 10,000 samples per day using minimal operator assistance. Thus, any technique for strontium analysis for use by CDC must involve reusable equipment, and be rapid, automated, and predictable.
Attempts to concentrate and purify 90Sr from urine using a single strontium ion extraction chromatographic resin (also referred to herein as a “strontium extraction resin”) have been hampered by the other ionic components of urine, particularly alkali metal ions which are present in much higher concentrations (e.g., 40 to 100 mM) than strontium (typically less than 10 picomolar, pM). Removing quenchers and/or separating the strontium from the quenchers and materials that interfere with Sr isolation (e.g., alkali metal ions) can be cumbersome and time consuming. Consequently, there is an ongoing need for new methods for rapidly and efficiently extracting and concentrating strontium from urine so that 90Sr concentrations can be determined without interference from other components found in urine. The present invention addresses this need.